Mitochondrial VOLTAGE-DEPENDENT ANION CHANNEL 3 regulates stomatal closure by abscisic acid signaling.

In Arabidopsis (Arabidopsis thaliana), stomatal closure mediated by abscisic acid (ABA) is redundantly controlled by ABA receptor family proteins (PYRABACTIN RESISTANCE 1 [PYR1]/PYR1-LIKE [PYLs]) and subclass III SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASES 2 (SnRK2s). Among these proteins, the roles of PYR1, PYL2, and SnRK2.6 are more dominant. A recent discovery showed that ABA-induced accumulation of reactive oxygen species (ROS) in mitochondria promotes stomatal closure. By analyzing stomatal movements in an array of single and higher order mutants, we revealed that the mitochondrial protein VOLTAGE-DEPENDENT ANION CHANNEL 3 (VDAC3) jointly regulates ABA-mediated stomatal closure with a specialized set of PYLs and SnRK2s by affecting cellular and mitochondrial ROS accumulation. VDAC3 interacted with 9 PYLs and all 3 subclass III SnRK2s. Single mutation in VDAC3, PYLs (except PYR1 and PYL2), or SnRK2.2/2.3 had little effect on ABA-mediated stomatal closure. However, knocking out PYR1, PYL1/2/4/8, or SnRK2.2/2.3 in vdac3 mutants resulted in significantly delayed or attenuated ABA-mediated stomatal closure, despite the presence of other PYLs or SnRK2s conferring redundant functions. We found that cellular and mitochondrial accumulation of ROS induced by ABA was altered in vdac3pyl1 mutants. Moreover, H2O2 treatment restored ABA-induced stomatal closure in mutants with decreased stomatal sensitivity to ABA. Our work reveals that VDAC3 ensures redundant control of ABA-mediated stomatal closure by canonical ABA signaling components.

Tumor-associated neutrophils suppress CD8+ T cell immunity in urothelial bladder carcinoma through the COX-2/PGE2/IDO1 Axis.

BACKGROUND: Many urothelial bladder carcinoma (UBC) patients don't respond to immune checkpoint blockade (ICB) therapy, possibly due to tumor-associated neutrophils (TANs) suppressing lymphocyte immune response. METHODS: We conducted a meta-analysis on the predictive value of neutrophil-lymphocyte ratio (NLR) in ICB response and investigated TANs' role in UBC. We used RNA-sequencing, HALO spatial analysis, single-cell RNA-sequencing, and flow cytometry to study the impacts of TANs and prostaglandin E2 (PGE2) on IDO1 expression. Animal experiments evaluated celecoxib's efficacy in targeting PGE2 synthesis. RESULTS: Our analysis showed that higher TAN infiltration predicted worse outcomes in UBC patients receiving ICB therapy. Our research revealed that TANs promote IDO1 expression in cancer cells, resulting in immunosuppression. We also found that PGE2 synthesized by COX-2 in neutrophils played a key role in upregulating IDO1 in cancer cells. Animal experiments showed that targeting PGE2 synthesis in neutrophils with celecoxib enhanced the efficacy of ICB treatment. CONCLUSIONS: TAN-secreted PGE2 upregulates IDO1, dampening T cell function in UBC. Celecoxib targeting of PGE2 synthesis represents a promising approach to enhance ICB efficacy in UBC.

Stacked Covalent Organic Ribbons Perpendicular to Graphene Oxide Sheets; a 1D-p-2D Design for Photocatalytic Tandem Reactions.

Development of one dimensional covalent organic frameworks (1D-COFs) with potential in light absorption and catalysis is still challenging, due to their rapid interpenetration to form 2D and 3D porous structures. Here we report a successful synthesis of imine-linked 1D covalent organic ribbons (COR), using two simple linear building blocks 1,4-Benzenediamine (Bda) and [2,2'-Bipyridine]-5,5'-dicarbaldehyde (Bpy). The obtained 1D structure with nanorod morphology could keep its physicochemical characteristic properties when it is perpendicular to the surface of graphene oxide (GO) sheets (1D-p-2D structure). Due to an AB π- π stacking and efficient charge transfer between perpendicular 1D COR and GO sheets, the obtained nanocomposite showed strong visible light absorbance (400-700 nm) with coefficient of 4.400 M-1 cm-1 and decreased recombination rate of photogenerated reactive species by 92 %. The strategy of 1D-p-2D light driven system greatly enhanced the photocatalytic activity in practical applications such as both oxidation and hydrogenation tandem reactions to a rate constant of higher than 0.02 min-1 . This study presents the first case of 1D covalent organic polymers grown perpendicularly on a carbon-based layer for boosting electron mobility through the junction between the two components.

Effects of Non-invasive Brain Stimulation on Hereditary Ataxia: a Systematic Review and Meta-analysis.

Numerous studies have demonstrated the potential of non-invasive brain stimulation (NIBS) techniques as a viable treatment option for cerebellar ataxia. However, there is a notable dearth of research investigating the efficacy of NIBS specifically for hereditary ataxia (HA), a distinct subgroup within the broader category of cerebellar ataxia. This study aims to conduct a comprehensive systematic review and meta-analysis in order to assess the efficacy of various NIBS methods for the treatment of HA. A thorough review of the literature was conducted, encompassing both English and Chinese articles, across eight electrical databases. The focus was on original articles investigating the therapeutic effectiveness of non-invasive brain stimulation for hereditary ataxia, with a publication date prior to March 2023. Subsequently, a meta-analysis was performed specifically on randomized controlled trials (RCTs) that fulfilled the eligibility criteria, taking into account the various modalities of non-invasive brain stimulation. A meta-analysis was conducted, comprising five RCTs, which utilized the Scale for the Assessment and Rating of Ataxia (SARA) as the outcome measure to evaluate the effects of transcranial magnetic stimulation (TMS). The findings revealed a statistically significant mean decrease of 1.77 in the total SARA score following repetitive TMS (rTMS) (p=0.006). Subgroup analysis based on frequency demonstrated a mean decrease of 1.61 in the total SARA score after high-frequency rTMS (p=0.05), while no improvement effects were observed after low-frequency rTMS (p=0.48). Another meta-analysis was performed on three studies, utilizing ICARS scores, to assess the impact of rTMS. The results indicated that there were no statistically significant differences in pooled ICARS scores between the rTMS group and the sham group (MD=0.51, 95%CI: -5.38 to 6.39; p=0.87). These findings align with the pooled results of two studies that evaluated alterations in post-intervention BBS scores (MD=0.74, 95%CI: -5.48 to 6.95; p=0.82). Despite the limited number of studies available, this systematic review and meta-analysis have revealed promising potential benefits of rTMS for hereditary ataxia. However, it is strongly recommended that further high-quality investigations be conducted in this area. Furthermore, the significance of standardized protocols for NIBS in future studies was also emphasized.

Identification of an IDO1-based immune classifier for survival prediction of upper tract urothelial carcinoma.

The limited response rate of immunotherapy in upper tract urothelial carcinoma (UTUC) might be attributed to additional immunosuppressive mechanisms in vivo. As a promising immune checkpoint target, the expression and prognostic role of indoleamine 2,3-dioxygenase 1 (IDO1) in UTUC remains unknown. In this study, the expression and prognostic value of IDO1 was analyzed in 251 patients from 3 independent cohorts. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to construct an IDO1-based immune classifier and external validation was performed to further validate the classifier. RNA sequencing and immunofluorescence were used to explore the immune contexture of different risk groups stratified by classifier. We found that high IDO1 expression on tumor cells (TC) indicated a poorer overall survival and disease-free survival in all cohorts. Patients with high expression of IDO1 TC possessed increased infiltration of CD4+ , CD8+ and Foxp3+ T cells. An immune classifier based on intratumoral CD8+ lymphocytes, IDO1 TC, and stromal PD-L1 expression status was developed, with its area under the curves (AUCs) values for overall survival at 5 y being 0.79 (95% confidence interval [CI] 0.65-0.93) in the discovery cohort, 0.75 (95% CI 0.58-0.92) and 0.78 (95% CI 0.65-0.92) in the internal and external validation cohorts, respectively. The high-risk group stratified by the immune classifier was associated with immunosuppressive contexture, accompanied by enhanced CD8+ T cells exhaustion patterns. Our IDO1-based immune classifier can provide a superior accuracy for survival prediction and lead to individual stratification of UTUC immune subtypes.

The Kelch-F-box protein SMALL AND GLOSSY LEAVES 1 (SAGL1) negatively influences salicylic acid biosynthesis in Arabidopsis thaliana by promoting the turn-over of transcription factor SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1).

Salicylic acid (SA) is a key phytohormone regulating plant immunity. Although the transcriptional regulation of SA biosynthesis has been well-studied, its post-translational regulation is largely unknown. We report that a Kelch repeats-containing F-box (KFB) protein, SMALL AND GLOSSY LEAVES 1 (SAGL1), negatively influences SA biosynthesis in Arabidopsis thaliana by mediating the proteolytic turnover of SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1), a master transcription factor that directly drives SA biosynthesis during immunity. Loss of SAGL1 resulted in characteristic growth inhibition. Combining metabolomic, transcriptional and phenotypic analyses, we found that SAGL1 represses SA biosynthesis and SA-mediated immune activation. Genetic crosses to mutants that are deficient in SA biosynthesis blocked the SA overaccumulation in sagl1 and rescued its growth. Biochemical and proteomic analysis identified that SAGL1 interacts with SARD1 and promotes the degradation of SARD1 in a proteasome-dependent manner. These results unravelled a critical role of KFB protein SAGL1 in maintaining SA homeostasis via controlling SARD1 stability.

Sorafenib-Loaded Copper Peroxide Nanoparticles with Redox Balance Disrupting Capacity for Enhanced Chemodynamic Therapy against Tumor Cells.

Chemodynamic therapy (CDT) is a promising hydroxyl radical (•OH)-mediated tumor therapeutic method with desirable tumor specificity and minimal side effects. However, the efficiency of CDT is restricted by the pH condition, insufficient H2O2 level, and overexpressed reductive glutathione (GSH), making it challenging to solve these problems simultaneously to improve the efficacy of CDT. Herein, a kind of polyvinylpyrrolidone-stabilized, sorafenib-loaded copper peroxide (CuO2-PVP-SRF) nanoparticle (NPs) was designed and developed for enhanced CDT against tumor cells through the synergetic pH-independent Fenton-like, H2O2 self-supplying, and GSH depletion strategy. The prepared CuO2-PVP-SRF NPs can be uptaken by 4T1 cells to specifically release Cu2+, H2O2, and SRF under acidic conditions. The intracellular GSH can be depleted by SRF-induced system xc- dysfunction and Cu2+-participated redox reaction, causing the inactivation of GPX4 and generating Cu+. A great amount of •OH was produced in this reducing capacity-disrupted condition by the Cu+-mediated Fenton-like reaction, causing cell apoptosis and lipid hydroperoxide accumulation-induced ferroptosis. They display an excellent 4T1 cell killing outcome through the improved •OH production capacity. The CuO2-PVP-SRF NPs display elevated therapeutic efficiency of CDT and show good promise in further tumor treatment applications.

Maximum Spreading of Impacting Ferrofluid Droplets under the Effect of Nonuniform Magnetic Field.

This article investigates the maximum spreading of ferrofluid droplets impacting on a hydrophobic surface under nonuniform magnetic fields. A generalized model for scaling the maximum spreading is developed. It is observed that, if the magnetic field strength is zero, a ferrofluid droplet not only demonstrates similar spreading dynamics as the water droplet but also obeys the same scaling law for the maximum spreading factor. Therefore, this article emphasizes the effects of magnetic field strength. In this regard, a dimensionless parameter (Nm) is introduced as the ratio between inertial force and Kelvin force, with an assumption that the kinetic energy mainly transforms to thermal energy. This parameter allows us to rescale all experimental data on a single curve with the Padé approximant, which is applicable to a wide range of impact velocities and magnetic field strengths.

Growth of wrinkle-free and ultra-flat Bi-layer graphene on sapphire substrate using Cu sacrificial layer.

The transfer process of chemical vapor deposition graphene film leads to unavoidable crack, wrinkles, doping, and contamination, which limits its function to establish stable and high-performance devices. It raises a growing interest to fabricate high-quality graphene on the target substrate directly. Here, bi-layer graphene (BLG) film can be grown on sapphire substrate by a Cu sacrificial layer using atmospheric-pressure chemical vapor deposition. The as-obtained BLG at the interface between sapphire and Cu layer is free of wrinkles, and the corresponding surface roughness Ra is as low as 0.66 nm. The square resistance of the graphene is 898.1 ohm sq-1, which is the lowest among the records of graphene film directly grown on nonmetal substrates.

Is salvage radiotherapy optimal to patients with occult cervical cancer undergoing inadvertent simple hysterectomy? A propensity score-matched analysis of a nationwide clinical oncology database.

OBJECTIVE: We used National Cancer Institute's Surveillance, Epidemiology and End Result database to assess the role of salvage radiotherapy for women with unanticipated cervical cancer after simple hysterectomy. METHODS: Patients with non-metastatic cervical cancer and meeting inclusion criteria were divided into three groups based on treatment strategy: simple hysterectomy, salvage radiotherapy after hysterectomy and radical surgery. Parallel propensity score-matched datasets were established for salvage radiotherapy group vs. simple hysterectomy group (matching ratio 1: 1), and salvage radiotherapy group vs. radical surgery group (matching ratio 1:2). The primary endpoint was the overall survival advantage of salvage radiotherapy over simple hysterectomy or radical surgery within the propensity score-matched datasets. RESULTS: In total, 2682 patients were recruited: 647 in the simple hysterectomy group, 564 in the salvage radiotherapy group and 1471 in the radical surgery group. Age, race, histology, grade, FIGO stage, insured and marital status and chemotherapy were comprised in propensity score-matched. Matching resulted in two comparison groups with neglectable differences in most variables, except for black race, FIGO stage III and chemotherapy in first matching. In the matched analysis for salvage radiotherapy vs. simple hysterectomy, the median follow-up time was 39 versus 32 months. In the matched analysis for salvage radiotherapy vs. radical surgery, the median follow-up time was 39 and 41 months, respectively. Salvage radiotherapy (HR 0.53, P = 0.046) significantly improved overall survival compared with simple hysterectomy, while salvage radiotherapy cannot achieve similar overall survival to radical surgery (HR 1.317, P = 0.045). CONCLUSIONS: This is the largest study of the effect of salvage radiotherapy on overall survival in patients with unanticipated cervical cancer. Salvage radiotherapy can improve overall survival compared with hysterectomy alone, while cannot achieve comparable survival to radical surgery.

Neoadjuvant chemotherapy followed by radical surgery versus concurrent chemoradiotherapy in patients with FIGO stage IIB cervical cancer: the CSEM 006 study.

BACKGROUND: Concurrent chemoradiotherapy is the first-line treatment for FIGO stage IIB cervical cancer. Neoadjuvant chemotherapy followed by radical surgery may provide another treatment option. PRIMARY OBJECTIVE: To compare the therapeutic outcomes of neoadjuvant chemotherapy followed by surgery with cisplatin-based concurrent chemoradiotherapy for stage IIB cervical cancer. STUDY HYPOTHESIS: We hypothesize that the therapeutic effect of neoadjuvant chemotherapy combined with surgery and risk-adapted adjuvant treatment will be superior to that of concurrent chemoradiotherapy in stage IIB cervical cancer. TRIAL DESIGN: Patients with stage IIB cervical cancer will be randomized 1:1 to neoadjuvant chemotherapy followed by surgery (Arm A) or concurrent chemoradiotherapy (Arm B). In arm A, patients will receive three cycles of paclitaxel and cisplatin followed by a type C radical hysterectomy and pelvic ±paraaortic lymphadenectomy. Patients showing progression after neoadjuvant chemotherapy will be referred to concurrent chemoradiotherapy. Adjuvant therapy will be recommended according to the presence of pathological risks. In Arm B, all patients will receive definitive concurrent chemoradiotherapy, including external beam pelvic radiotherapy combined with concurrent weekly cisplatin followed by brachytherapy. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients between 18 and 60 years with histologically confirmed, untreated stage IIB cervical squamous carcinoma, adenocarcinoma, or adeno-squamous carcinoma. PRIMARY ENDPOINT: The primary endpoint is 2-year disease-free survival. SAMPLE SIZE: An estimated sample size of 240 is required to fulfill the study objectives. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: As of February 2020, 115 eligible patients from four institutions have been enrolled. Enrollment is expected to be completed by December 2022. TRIAL REGISTRATION NUMBER: ClinicalTrials. gov identifier: NCT02595554.

Secular trends in sedentary behaviors and associations with weight indicators among Chinese reproductive-age women from 2004 to 2015: findings from the China Health and Nutrition Survey.

BACKGROUND: Overweight and obesity are rising among Chinese reproductive-age women, while some studies have focused on the relationship between sedentary behavior and obesity in certain populations, none has focused on Chinese reproductive-age women specifically. This study examined secular trends in leisure time sedentary behaviors (watching television time, computer time and reading time, and the total sedentary time) among Chinese reproductive-age women and the association of those behaviors with five weight indicators-body mass index (BMI), waist circumference (WC) and overweight, obesity, and abdominal obesity status. METHODS: A prospective cohort study was conducted with Chinese reproductive-age women aged 15-49 who had participated in two or more rounds of the China Health and Nutrition Survey (CHNS), and completed the questionnaire and anthropometric measurements. The exposure variables were the average weekly time spent on three leisure time sedentary behaviors (watching television, using computer, and reading) and the total sedentary time (the sum of the above three sedentary time and video game time). Mixed-effect linear models were produced to explore the secular trends of the mean hours of these sedentary behaviors and the total sedentary time after adjusting covariates. Models were also produced to study the effects of these types of sedentary behavior levels on BMI and WC. Mixed-effect logistic regression models were produced to study the effects of the sedentary behavior levels on overweight, obesity, and abdominal obesity status. RESULTS: The total sedentary time among the reproductive-age women increased over time across most of age, region, educational levels, and income groups from 2004 to 2015. Television hours fluctuated, it increased and then declined over time across most of age, region, and income groups. Computer hours continually increased over time across all age, region, educational level, and income groups. Reading hours gradually decreased over time across most of age, region, educational level, and income groups. Those with a moderate level of television time (14 to <35 h/week) had 1.08 cm larger WCs and were 1.31 times more likely to have abdominal obesity than those with a low level of television time (<14 h/week). Those with a high level of television time (≥35 h/week) had 1.74 cm larger WCs, 0.66 kg/m2 larger BMIs, were 1.50 times more likely to be overweight and were 1.47 times more likely to have abdominal obesity than those with a low level of television time (<14 h/week). Greater computer, reading time, and total sedentary time were not associated with WC, BMI, overweight, obesity, or abdominal obesity. CONCLUSIONS: These findings showed that among Chinese reproductive-age women ages 15-49, secular trends of computer time increased rapidly, reading time decreased gradually and television time fluctuated but showed not much difference from 2004 to 2015. The sharp increase in computer time far outweighed the decline in reading time. As a result, the overall sedentary behavior time of Chinese reproductive-age women gradually increased. These findings provided strong evidence that greater television time was significantly associated with higher BMI, WC, and higher risks of overweight, abdominal obesity among Chinese reproductive-age women. Computer, reading, and the total sedentary time were not associated with those weight indicators.

Upregulation of microRNA-328-3p by hepatitis B virus contributes to THLE-2 cell injury by downregulating FOXO4.

BACKGROUND: Hepatitis B virus (HBV) remains a major cause of chronic hepatitis and hepatocellular carcinoma, and miRNAs play important roles in HBV pathogenesis. Our previous study has shown that miR-328-3p is upregulated in HBV-infected patients and serves as a potent predictor for the prognosis of HBV-related liver failure. METHODS: Here, the role of miR-328-3p in modulating cell injury in HBV-infected liver cells THLE-2 was investigated in detail. MiR-328-3p expression was examined using qRT-PCR. The levels of pro-inflammatory cytokines were measured using ELISA. HBV RNA and HBV DNA levels were quantified. The interactions between STAT3 and miR-328-3p promoter as well as miR-328-3p and FOXO4 were analyzed using chromatin immunoprecipitation (CHIP) assay and luciferase reporter assay, respectively. THLE-2 cell injury was evaluated by examining cell viability and apoptosis. RESULTS: HBV promoted expression of miR-328-3p through the STAT3 signal pathway and that increasingly expressed miR-328-3p downregulated its target FOXO4, leading to the promotion of cell injury in HBV-infected liver cells THLE-2. CONCLUSION: These data demonstrate that HBV-STAT3-miR-328-3p-FOXO4 regulation pathway may play an important role in the pathogenesis of HBV infection.

Small cell carcinoma of the uterine cervix: a multi-institutional experience.

OBJECTIVE: Small cell carcinoma of the uterine cervix is associated with a poor prognosis with a median overall survival that is quite low. The aim of this study was to determine the clinico-pathologic characteristics that have an impact on survival in patients with small cell carcinoma of the uterine cervix. METHODS: A total of 93 patients were involved in this retrospective study. Inclusion criteria were patients diagnosed with histopathologically confirmed small cell carcinoma of the uterine cervix and then later treated at three participating centers, between June 2001 and March 2015. Those without complete available follow-up records were excluded. The endpoints of this study were disease-free survival and overall survival. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS: There were statistical differences in overall survival between patients in early and in advanced stages by using the 2009 International Federation of Gynecology and Obstetrics (FIGO) clinical stage. There were 75 patients with FIGO stage I to IIA (56 patients stage I, 17 patients stage IIA, and two patients stage IB or IIA because of uncertainty as to whether the fornix was involved); and 18 patients with FIGO stage IIB and above (10 patients IIB stage, five patients stage III, and three patients stage IV). Among the 76 patients who had surgery, 73 (96%) had a radical hysterectomy with pelvic lymph node dissection and three (4%) patients had a simple hysterectomy without lymph node dissection. For early-stage patients, the 5 year disease-free survival rate was 52.7% compared with 32.4% in the advanced stage group (p=0.022). The disease-free survival for the early-stage group was 64.4% compared with 36.7% in the advanced-stage group (p=0.047). For factors affecting overall survival, age at diagnosis, tumor homology, tumor size, depth of stromal invasion, lymph node involvement, and treatment modality failed to reach significance in both univariate and multivariate analysis. CONCLUSION: FIGO stage was a prognostic factor impacting survival-both overall survival and disease-free survival. Age at diagnosis, tumor histology (pure or mixed), tumor size, depth of stromal invasion, lymph node involvement, and treatment modality did not have an impact on overall survival.

LncRNA HOTAIRM1 promotes osteogenesis by controlling JNK/AP-1 signalling-mediated RUNX2 expression.

Mesenchymal stem cells (MSCs) have potential ability to differentiate into osteocytes in response to in vitro specific induction. However, the molecular basis underlying this biological process remains largely unclear. In this study, we identify lncRNA HOTAIRM1 as a critical regulator to promote osteogenesis of MSCs. Loss of HOTAIRM1 significantly inhibits the calcium deposition and alkaline phosphatase activity of MSCs. Mechanistically, we find that HOTAIRM1 positively modulates the activity of JNK and c-Jun, both of which are widely accepted as crucial regulators of osteogenic differentiation. More importantly, c-Jun is found to be functionally involved in the regulation of RUNX2 expression, a master transcription factor of osteogenesis. In detail, c-Jun can help recruit the acetyltransferase p300 to RUNX2 promoter, facilitating acetylation of histone 3 at K27 site, therefore epigenetically activating RUNX2 gene transcription. In summary, this study highlights the functional importance of HOTAIRM1 in regulation of osteogenesis, and we characterize HOTAIRM1 as a promising molecular target for bone tissue repair and regeneration.

Quantum tomography of the photon-plasmon conversion process in a metal hole array.

In the past decades, quantum plasmonics has become an active area due to its potential applications in on-chip plasmonic devices for quantum information processing. However, the fundamental physical process, i.e., how a quantum state of light evolves in the photon-plasmon conversion process, has not been described by a detailed microscopic quantum model. Here, we report a complete characterization of the plasmon-assisted extraordinary optical transmission process through quantum process tomography. By inputting various coherent states to interact with the plasmonic structure and detecting the output states with a homodyne detector, we reconstruct the process tensor of the photon-plasmon conversion process. Both the amplitude and phase information of the process are extracted, which explain the evolution of the quantum-optical state after the coupling with plasmons. Our experimental demonstration constitutes a fundamental block for future on-chip applications of quantum plasmonic circuits.

Knockdown of PKM2 enhances radiosensitivity of cervical cancer cells.

BACKGROUND: Pyruvate kinase isozyme type M2 (PKM2) catalyzes the final step in glycolysis and has been found to be up-regulated in multiple human malignancies. However, whether PKM2 regulates the radiosensitivity of human cervical cancer (CC) remains unknown. METHODS: The expression of PKM2 in 94 patients with CC in the complete response (CR) and noncomplete response (nCR) groups, was evaluated by immunohistochemistry. The effect of PKM2 inhibition on radiosensitivity, the cell cycle, DNA damage, and apoptosis was evaluated by immunofluorescence analysis, colony formation assay, flow cytometry analysis and Western blotting. RESULTS: PKM2 expression was more highly expressed in the nCR group than that in CR group and PKM2 expression was enhanced in CC cells after ionizing radiation (IR). In addition, knockdown of PKM2 combined with IR significantly reduced cell growth, promoted apoptosis, and enhanced radiosensitivity. Additionally, knockdown of PKM2 with IR resulted in increased phosphorylation of DNA repair checkpoint proteins (ATM) and phosphorylated-H2AX. Moreover, knockdown of PKM2 combined with IR significantly increased the expression of cleaved caspase 3 and caspase 9, whereas Bcl2 expression was suppressed. Furthermore, knockdown of PKM2 combined with IR markedly reduced the expression of several cancer stem cell biomarkers in vitro, including NANOG, OCT4, SOX2, and Bmi1. CONCLUSIONS: The results of our study suggests that PKM2 might be involved in mediating CC radiosensitivity and is identified as a potentially important target to enhance radiosensitivity in patients with CC.

[Expressions of miR-146a and miR-155 in different samples of chronic hepatitis B patients].

OBJECTIVE: To detect the levels of miR-146a and miR-155 in different samples from chronic hepatitis B (CHB), reveal whether there is a correlation between the 2 miRNAs in different samples, and to provide a theoretical basis for sample choice of miRNA research in liver.
 Methods: Real-time PCR was conducted to examine the expression of miR-146a and miR-155 in the plasma, peripheral blood mononuclear cell (PBMC), and liver tissues from 41 CHB patients who underwent nucleoside analogues antiviral therapy for 104 weeks. Correlations between the levels of miR-146a and miR-155 among the 3 samples were analyzed.
 Results: The expressions of miR-146a and miR-155 in the plasma, PBMC and liver tissues were significantly down-regulated at the 104th week than those at the baseline (all P<0.05). There was a correlation in the expression of miR-146a between plasma and liver tissues (r=0.560, P=0.007), PBMC and liver tissues (r=0.428, P=0.047) at baseline. There was a correlation in the expression of miR-155 between plasma and liver tissue (r=0.587, P=0.004), PBMC and liver tissue (r=0.483, P=0.023) at baseline. The expressions of miR-146a and miR-155 between the plasma and PBMC were not correlated (P>0.05).
 Conclusion: Compared with PBMC, miR-146a and miR-155 from plasma can better reflect the expression in the liver tissues, suggesting that plasma can be applied in the mechanism research on miR-146a and miR-155 in the liver diseases instead of liver tissues.

Distinct Effects of miR-210 Reduction on Neurogenesis: Increased Neuronal Survival of Inflammation But Reduced Proliferation Associated with Mitochondrial Enhancement.

Neurogenesis is essential to brain development and plays a central role in the response to brain injury. Stroke and head trauma stimulate proliferation of endogenous neural stem cells (NSCs); however, the survival of young neurons is sharply reduced by postinjury inflammation. Cellular mitochondria are critical to successful neurogenesis and are a major target of inflammatory injury. Mitochondrial protection was shown to improve survival of young neurons. This study tested whether reducing cellular microRNA-210 (miR-210) would enhance mitochondrial function and improve survival of young murine neurons under inflammatory conditions. Several studies have demonstrated the potential of miR-210 inhibition to enhance and protect mitochondrial function through upregulation of mitochondrial proteins. Here, miR-210 inhibition significantly increased neuronal survival and protected the activity of mitochondrial enzymes cytochrome c oxidase and aconitase in differentiating NSC cultures exposed to inflammatory mediators. Unexpectedly, we found that reducing miR-210 significantly attenuated NSC proliferation upon induction of differentiation. Further investigation revealed that increased mitochondrial function suppressed the shift to primarily glycolytic metabolism and reduced mitochondrial length characteristic of dividing cells. Activation of AMP-regulated protein kinase-retinoblastoma signaling is important in NSC proliferation and the reduction of this activation observed by miR-210 inhibition is one mechanism contributing to the reduced proliferation. Postinjury neurogenesis occurs as a burst of proliferation that peaks in days, followed by migration and differentiation over weeks. Our studies suggest that mitochondrial protective miR-210 inhibition should be delayed until after the initial burst of proliferation, but could be beneficial during the prolonged differentiation stage.SIGNIFICANCE STATEMENT Increasing the success of endogenous neurogenesis after brain injury holds therapeutic promise. Postinjury inflammation markedly reduces newborn neuron survival. This study found that enhancement of mitochondrial function by reducing microRNA-210 (miR-210) levels could improve survival of young neurons under inflammatory conditions. miR-210 inhibition protected the activity of mitochondrial enzymes cytochrome c oxidase and aconitase. Conversely, we observed decreased precursor cell proliferation likely due to suppression of the AMP-regulated protein kinase-retinoblastoma axis with miR-210 inhibition. Therefore, mitochondrial protection is a double-edged sword: early inhibition reduces proliferation, but inhibition later significantly increases neuroblast survival. This explains in part the contradictory published reports of the effects of miR-210 on neurogenesis.

Identification, synthesis and regulatory function of the N-acylated homoserine lactone signals produced by Pseudomonas chlororaphis HT66.

BACKGROUND: Pseudomonas chlororaphis HT66 isolated from the rice rhizosphere is an important plant growth-promoting rhizobacteria that produce phenazine-1-carboxamide (PCN) in high yield. Phenazine production is regulated by a quorum sensing (QS) system that involves the N-acylated homoserine lactones (AHLs)-a prevalent type of QS molecule. RESULTS: Three QS signals were detected by thin layer chromatography (TLC) and high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS), which identified to be N-(3-hydroxy hexanoyl)-L-homoserine lactone (3-OH-C6-HSL), N-(3-hydroxy octanoyl)-L-homoserine lactone (3-OH-C8-HSL) and N-(3-hydroxy decanoyl)-L-homoserine lactone (3-OH-C10-HSL). The signal types and methods of synthesis were different from that in other phenazine-producing Pseudomonas strains. By non-scar deletion and heterologous expression techniques, the biosynthesis of the AHL-signals was confirmed to be only catalyzed by PhzI, while other AHLs synthases i.e., CsaI and HdtS were not involved in strain HT66. In comparison to wild-type HT66, PCN production was 2.3-folds improved by over-expression of phzI, however, phzI or phzR mutant did not produce PCN. The cell growth of HT66∆phzI mutant was significantly decreased, and the biofilm formation in phzI or phzR inactivated strains of HT66 decreased to various extents. CONCLUSION: In conclusion, the results demonstrate that PhzI-PhzR system plays a critical role in numerous biological processes including phenazine production.